Our objective was to understand the relationship between mental health screening results, health disparity, and STI risk among detained adolescents. In this 24-month cross-sectional study of 1,181 detainees (age 13-18 years), we examined associations between race, gender, mental health screening results (as measured by the Massachusetts Youth Screening Instrument-2nd Edition) and sexually transmitted infection rates (STI; chlamydia, gonorrhea, and trichomonas). Consistent with previous research, females and black youth were disproportionately affected by STI. Race and gender differences were also noted in mental health screening. The odds of having an STI increased by 23% (OR = 1.23, 95% CI = 1.06, 1.37) with each one-unit increase in the alcohol/drug subscale score for females. Gender-specific STI interventions for detained youth are warranted. For young women with substance abuse, specific interventions are necessary and may help reduce health disparity in this vulnerable population.